1. Field of the Invention
The invention relates to an osmotically driven fluid dispenser which is activated after being exposed to an aqueous environment. The dispenser can be programmed to begin delivering a fluid, such as a drug solution or a drug suspension, after a predetermined delay period following introduction of the dispenser into the aqueous environment.
2. Description of the Prior Art
The present invention provides an improved osmotically driven fluid dispenser of the type described in commonly owned U.S. Pat. Nos. 3,987,790; 3,995,631 and 4,034,756. These patents describe mini-osmotic pumps. Mini-osmotic pumps generally comprise a semipermeable wall which encloses either an osmotic solute or a combination of an osmotic solute and a beneficial agent such as a drug. An orifice is provided through the semipermeable wall. When the pump is placed in a aqueous environment, water permeates through the wall and dissolves the osmotic agent and/or beneficial agent. The solution of the osmotic agent and/or beneficial agent is then pumped through the delivery orifice as fresh incoming water enters the pump.
The mini-osmotic pumps disclosed in the three above-identified U.S. Patents separate the osmotically effective solute from the drug. The pumps disclosed in these patents additionally include an inner flexible bag that holds the drug charge. The osmotically effective solute composition (e.g., an inorganic salt) is present as an intermediate layer encapsulating the bag. The outer shape-retaining membrane is at least in part permeable to water and encapsulates both the layer of osmotically effective solute composition and the bag. A plug seals the open end of the bag, and a filling/discharge port in the plug communicates with the interior of the bag.
In operation the bag is filled with drug solution via the filling/discharge port and placed in an aqueous environment, such as a body cavity or within body tissue. Water is imbibed from the environment by the osmotically effective solute through the membrane into the space between the inner flexible bag and the membrane. Since the bag is flexible and the membrane is rigid, the imbibed water squeezes the bag inwardly, thereby displacing drug out the filling/discharge port.
Generally, the mini-osmotic pumps of the prior art are activated upon exposure to an aqueous environment. The pumps begin dispensing their contents after water from the environment has permeated through the outer semipermeable membrane. Thus, any delay between the time when the mini-osmotic pump is placed in an aqueous environment and the time when the pump begins dispensing its contents is determined primarily by one or more of the following parameters: (1) the permeation characteristics of the semipermeable membrane; (2) the thickness of the semipermeable membrane; (3) any exterior coating on the semipermeable membrane; (4) the composition of the osmotically effective solute and its osmotic imbibition properties; and (5) the mechanical properties of the drug/osmotic agent reservoir.
Unfortunately, designing a pump with a pre-programmed drug delivery activation period based on one or more of the five above listed properties has proven to be disadvantageous from several respects. For example, in order to "program" a pump to begin dispensing drug after an initial activation period (e.g., a period of delay between the time when the pump is first placed in an aqueous environment and the time when the pump begins dispensing drug), pump designers have attempted to vary one or more of the physical properties of the semipermeable membrane wall. Unfortunately, while the semipermeable membrane wall properties do control the rate at which beneficial agents are dispensed from the pump, they do not provide much control over the initial activation period. For example, one can utilize a relatively impermeable membrane which only allows water to permeate through the pump wall very slowly. Unfortunately, this design severely restricts the rate at which the drug is dispensed from the device after the initial activation period. Another method of preprogramming the pump to begin delivering drug after an initial activation period is to increase the thickness of the outer semipermeable membrane. Unfortunately, this presents serious size limitations on the device, in particular when working with pumps of a size suited for swallowing or implanting in an animal or the human body.
One can also utilize an osmotic solute composition which only generates a low osmotic pressure gradient across the membrane, thereby causing water to permeate through the membrane at a very slow rate. Unfortunately, this design has very little effect on the initial activation period and also severely restricts the rate at which the drug is dispensed from the device after the initial activation period.
Finally, one can coat the semipermeable outer membrane of the pump with a bioerodible polymer. After the polymer erodes, the semipermeable membrane becomes exposed to the exterior aqueous environment. Unfortunately, it is very difficult to precisely control the rate at which a bioerodible polymer layer erodes. Furthermore, bioerodible polymers generally have the property of allowing a certain amount of water to be transported therethrough before they are fully eroded. This early water transport results in the pump dispensing a certain amount of drug or other beneficial agent before the desired activation period has fully expired.
Thus, there has been a need in the art for a mini-osmotic pump which can be "programmed" to deliver substantially no drug during a predetermined activation period and yet which can begin delivering the drug at a pharmaceutically acceptable rate after the initial activation period.